Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo.
The mouse model of liver ischemia and reperfusion injury has proven to be valuable for our understanding of the role that reactive oxygen and nitrogen metabolites play in postischemic tissue injury. This methods paper provides a detailed protocol for inducing partial liver ischemia followed by reperfusion. Liver ischemia is induced in anesthetized mice by cross-clamping the hepatic artery and portal vein for varying lengths of time, resulting in deprivation of blood flow to approximately 70% of the liver. Restoration of blood flow to the ischemic lobes enhances superoxide production concomitant with a rapid and marked decrease in the bioavailability of nitric oxide, resulting in alterations in the redox state of the liver in favor of a more oxidative environment. This hepatocellular oxidative stress induces the activation of oxidant-sensitive transcription factors followed by the upregulation of proinflammatory cytokines and mediators that ultimately lead to liver injury. This model can be induced in any strain or sex of mouse and requires 1-2 months of practice to become proficient in the surgery and animal manipulation. The roles of various reactive metabolites of oxygen and nitrogen may be evaluated using genetically engineered mice as well as selective molecular, cellular, and/or pharmacological agents.
Abe
Yuta
Y
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, 71130, USA.
Hines
Ian N
IN
Zibari
Gazi
G
Pavlick
Kevin
K
Gray
Laura
L
Kitagawa
Yuko
Y
Grisham
Matthew B
MB
D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood / Q000235:genetics; D000818:Animals; D017849:Animals, Inbred Strains; D001671:Biochemistry / Q000379:methods; D004195:Disease Models, Animal; D004789:Enzyme Activation; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D015202:Protein Engineering; D015424:Reperfusion / Q000295:instrumentation / Q000379:methods; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D013045:Species Specificity; D013482:Superoxide Dismutase; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D000099156:Superoxide Dismutase 2
D000410:Alanine Transaminase; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D013481:Superoxides; D014409:Tumor Necrosis Factor-alpha; D000099156:Superoxide Dismutase 2; C499090:Sod3 protein, mouse